Child’s Pulmonary Arterial Hypertension Appears to Be From New Gene Mutation

A case report from Texas Children’s Hospital described a 5-year-old boy with a newly identified mutation in the BMP9 gene leading to pulmonary arterial hypertension (PAH).

Many PAH cases are associated with genetic mutations, most frequently in the immune-related TGF-beta signaling pathways. BMP9 – also known as GDF2 – belongs to the bone morphogenic protein group, which are proteins included in the TGF-beta signaling pathways. Earlier studies have shown that BPM9 is involved in a condition called hereditary hemorrhagic telangiectasia (HHT), a vascular disorder that can have pulmonary hypertension features indistinguishable from idiopathic PAH.

The study, “Novel homozygous BMP9 nonsense mutation causes pulmonary arterial hypertension: a case report,” appeared in the journal BMC Pulmonary Medicine.

The research team, led by Guoliang Wang, reported that the child was 3 when admitted to the hospital with severe PAH and right heart failure, but with no signs of congenital heart disease. He had a severely dilated main pulmonary artery, as well as branch pulmonary arteries, and the heart had a dilated right atrium and left ventricle.

No family members had previously been affected by either PAH or HHT, and an examination of the boy’s parents showed that they were not affected by disease. Two years later, the child is now free of symptoms. He is treated with sildenafil, bosentan, treprostinil, and warfarin. The previous severely dilated main pulmonary artery and heart has recovered and shows only a mild dilation.

The team performed genetic analyses investigating coding regions and the boundaries between coding and non-coding regions of a large number of PAH associated genes, and discovered a new mutation in the form of a single amino acid change in the BMP9 gene. The boy had two copies of the faulty gene, and an analysis of the parents showed that they both had a copy each and were heterozygous carriers. The single amino acid change resulted in a stop signal being incorporated into the gene, leading to the production of just a short fragment of the protein.

Previous studies showed that enhancement of BMP9 signaling in the endothelium reverses PAH. The newly identified mutation suggests that BMP9 signaling is a crucial factor for PAH development, at least in some patients.